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1.
Chinese Medical Journal ; (24): 140-151, 2024.
Article in English | WPRIM | ID: wpr-1007742

ABSTRACT

Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.


Subject(s)
Humans , Receptors, Chimeric Antigen/therapeutic use , Neoplasm, Residual , Transplantation, Homologous/methods , Transplantation Conditioning/methods , Hematopoietic Stem Cell Transplantation/methods , Recurrence , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
2.
Chinese Journal of Laboratory Medicine ; (12): 458-463, 2023.
Article in Chinese | WPRIM | ID: wpr-995751

ABSTRACT

Objective:In order to determine the development potential of human embryos in vitro, amino acid and carnitine levels were measured in the culture medium of different grades of early human embryos. Methods:From the infertile couples who received in vitro fertilization-embryo transfer treatment in the Department of Reproductive Medicine of Linyi People′s Hospital from June 2022 to December 2022, the age of the women was defined as 25-35 years old [31.5(26.5, 33.25)] with 8-20 eggs, 126 cultured cells and embryos of the third day were randomly collected from infertile couples. They were divided into three groups according to the morphological level of the corresponding embryos: excellent, neutral and poor. Amino acids and L-carnitines levels in culture medium were detected by liquid chromatography-mass spectrometry (LC-MS). Using analysis of variance to compare differences among groups, correlation analysis, factor analysis was performed to analyze the association between the levels of amino acids and L-carnitines and development potential of early human embryos.Results:The value of Methionine/Phenylalanine was found statistically different among superior embryo (3.09±1.67), moderate embryo (4.00±1.19) and inferior embryo (4.99±2.04). The difference between the three groups was statistically different ( F=7.09, P<0.05): superior embryo vs moderate embryo ( t=-0.91, P<0.05), superior embryo vs inferior embryo ( t=-1.91, P<0.05), moderate embryo vs inferior embryo ( t=-0.99, P<0.05). Among different amino acids, Phe had the strongest positive correlation with Tyr ( r=0.99, P<0.01). Among different carnitines, C 8/C 10 has the strongest positive correlation with C 5DC+C 6OH/C 16( r=0.44, P<0.01). The weight value of leucine (isoleucine), arginine, valine/phenylalanine, glycine, tyrosine and carnitine(C 5DC+C 6OH)/C 8 calculated by the least square fitting model is 2.22, 1.99, 1.65, 1.54, 1.21 and 1.15 respectively. Conclusion:Leucine, arginine, valine/phenylalanine, glycine, tyrosine and carnitine (C 5DC+C 6OH)/C 8 in embryo culture medium were significantly correlated with the levels of early human embryos in vitro.

3.
Chinese Journal of Medical Genetics ; (6): 723-726, 2023.
Article in Chinese | WPRIM | ID: wpr-981815

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome.@*METHODS@#Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance.@*CONCLUSION@#The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.


Subject(s)
Male , Humans , Female , Lesch-Nyhan Syndrome/genetics , Pedigree , East Asian People , Heterozygote , Introns , Mutation
4.
Chinese Journal of Medical Genetics ; (6): 1566-1569, 2023.
Article in Chinese | WPRIM | ID: wpr-1009342

ABSTRACT

OBJECTIVE@#To explore the genetic characteristics of a child with mosaicism Turner syndrome.@*METHODS@#A child who had presented at Linyi People's Hospital on May 19, 2022 due to short stature was selected as the study subject. The child was subjected to combined chromosomal karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA).@*RESULTS@#The child was found to have a 46,X,i(X)(q10)[94]/45,X[6] karyotype. The result of FISH was nucish(XYpter,XYqter)1[78]/(XYpter)1,(XYqter)3[122]. CMA result for her peripheral blood sample was arr[hg19]Xp22.33p11.1(168551_58526888)×1, and that for her oral mucosal cells was arr[hg19]Xp22.33p11.1(168551_58526888)1-2,Xq11.2q28(63000001_155233098)×2-3. By integrating the above findings, her molecular karyotype was determined as mos 46,X,i(X)(q10)[94]/45,X[6].arr[hg19]Xp22.33p11.1(168551_58526888)×1-2,Xq11.2q28(63000001_155233098)×2-3.nucish(XYpter)1,(XYqter)3[122]/(XYpter,XYqter)1[78], which has indicated mosaicism Turner syndrome.@*CONCLUSION@#The 46,X,i(X)(q10)/45,X mosaicism probably underlay the pathogenesis in this child.


Subject(s)
Humans , Child , Female , Turner Syndrome/genetics , Mosaicism , In Situ Hybridization, Fluorescence , Karyotyping , Karyotype
5.
Journal of Leukemia & Lymphoma ; (12): 11-15, 2022.
Article in Chinese | WPRIM | ID: wpr-929724

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the main curable therapies for patients with acute lymphoblastic leukemia (ALL). This article discusses the status of allo-HSCT for ALL as well as how to combine targeted therapy with allo-HSCT to improve outcomes of ALL in the era of targeted therapy based on the data obtained from the 63rd American Society of Hematology (ASH) Annual Meeting.

6.
Chinese Journal of Laboratory Medicine ; (12): 777-782, 2022.
Article in Chinese | WPRIM | ID: wpr-958582

ABSTRACT

Chimeric antigen receptor(CAR)-T cell immunotherapy for refractory and relapsed acute lymphoblastic leukemia (R/R ALL) is one of the breakthroughs in the field of hematological malignant disease treatment. However, several challenges remain, such as immune rejection of allogeneic CAR-T cells, leukemia relapse, as well as could we apply CAR-T cell immunotherapy to ALL patients with positive measurable residual disease and those of newly diagnosed cases. The safety and efficiency of CAR-T therapy will be further improved for patients with ALL only by establishing appropriate strategies to address these challenges.

7.
Chinese Journal of Medical Genetics ; (6): 514-517, 2022.
Article in Chinese | WPRIM | ID: wpr-928448

ABSTRACT

OBJECTIVE@#To investigate the clinical phenotype and genetic diagnosis of an infant featuring multiple hair and hyperbilirubinemia.@*METHODS@#Conventional G-banding analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the patient were conducted, G-banding analyses of peripheral blood for the infant's parents were also performed.@*RESULTS@#We investigated an infant who carries a unbalanced, maternally inherited karyotype 46, X, der (X) t (X;1) (p11.22; q21.3) in which CMA and FISH analyses disclosed a 1q21.3q44 duplication of 93.03 Mb and Xp22.33p11.22 deletion of 54.53 Mb.@*CONCLUSION@#The phenotypes of this infant can probably be attributed to the 1q21.3q44 duplication and Xp22.33p11.22 deletion, which were maternally inherited.


Subject(s)
Humans , Chromosome Banding , Chromosome Deletion , Genetic Testing , In Situ Hybridization, Fluorescence , Karyotyping , Translocation, Genetic
8.
Chinese Journal of Internal Medicine ; (12): 806-811, 2021.
Article in Chinese | WPRIM | ID: wpr-911442

ABSTRACT

Objective:To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Method:Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF ( n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF ( n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result:Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P>0.05). According to once, the incidence of EBV viremia, defined as EBV>10 3 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively ( P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [ HR=1.022(95% CI 1.006-1.038),1.600(95% CI 1.059-2.418); P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)( P=0.005) and 10.1% (20/199) versus 8.0% (24/299) ( P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [ HR=1.908(95% CI 1.079-3.373),1.752(95% CI 1.161-2.643); P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P>0.05) between the two groups. Conclusion:Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.

9.
Journal of China Medical University ; (12): 250-254, 2019.
Article in Chinese | WPRIM | ID: wpr-744835

ABSTRACT

Objective To investigate the relationship between gene polymorphism of interleukin (IL) -1 and peri-implantitis. Methods A case-control experimental design was used in this study. Moreover, using a bioinformatics analysis, we selected three tagged single nucleotide polymorphisms (SNP) suitable for the Chinese population. Patients with peri-implantitis (n = 116) and 87 patients without peri-implantitis were included. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to tag SNP of IL-1α, IL-1β, and IL-1γn. Results The rs2856838 locus of the AA genotype of IL-1α was associated with a higher risk of implant periodontitis than the GG genotype. There was no statistical difference between the two groups with regard to the other SNP. Conclusion The AA genotype of rs2856838 is associated with periprosthetic inflammation.

10.
Frontiers of Medicine ; (4): 153-163, 2018.
Article in English | WPRIM | ID: wpr-772754

ABSTRACT

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3 Tcells, CD8 T cells, and CD19 B cells, and very slow in CD4 T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation.We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , China , Disease-Free Survival , Graft vs Host Disease , Allergy and Immunology , Mortality , HLA Antigens , Allergy and Immunology , Hematopoietic Stem Cell Transplantation , Immune Reconstitution , Reference Values , Siblings , T-Lymphocytes , Allergy and Immunology , Tissue Donors , Transplantation, Homologous
11.
Chinese Journal of Pathophysiology ; (12): 730-734, 2017.
Article in Chinese | WPRIM | ID: wpr-512744

ABSTRACT

AIM: To study the effects of fibroblast growth factor 8 (FGF8) on directional differentiation of human dental pulp stem cells (hDPSCs) into odontoblasts and pulp tissue.METHODS: hDPSCs were isolated and cultured, and identified with flow cytometry by detecting cell surface markers of hDPSCs.FGF8 at concentration of 50 μg/L was added into the mineralization fluid to induce the differentiation of the hDPSCs.The mRNA expression of dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), bone sialoprotein (BSP) and core-binding factor alpha 1 (Cbfa-1) in differentiated cells was detected by real-time PCR.FGF8 and mouse E11.5 dental epithelium formed restructuring cell group with hDPSCs, and then the restructuring cell group was transplanted under renal capsule membrane in nude mice for tissue culture.DNA in situ hybridization was used to identify the sources of odontoblasts and pulp cells.RESULTS: The surface markers of CD29 and CD90 showed positive in isolated hDPSCs.FGF8 induced hDPSCs to form a distinct mineralization nodule, and the expression of dentin-specific proteins, DSPP, BSP and Cbfa-1, was increased.hDPSCs were induced to differentiate into odontoblasts and pulp cells by E11.5 dental epithelium and FGF8.CONCLUSION: FGF8 can assist dental epithelium to induce directional differetiation of hDPSCs into odontoblasts and pulp cells, and formation of dentin and dental pulp cavity structure.

12.
Chinese Pharmacological Bulletin ; (12): 638-642, 2016.
Article in Chinese | WPRIM | ID: wpr-492454

ABSTRACT

Aim To investigate the sedative and hyp-notic effects of a novel compound H057 . Methods The sedative activity of H057 was investigated by re-cording the spontaneous locomotor activity in mice. The hypnotic property was evaluated by the latency and duration of loss of righting reflex( LORR) in mice and effect of H057 on the sleep onset in subthreshold dos-age of sodium pentobarbital treated mice. The extracel-lular levels of GABA and monoamine neurotransmitters in in cerebral cortex were measured by microdialysis in vivo. Results The spontaneous locomotor activity was decreased by 25% and 66% in H057 ( 5 , 25 mg · kg-1 ,i. p. ) treated mice, respectively. H057 ( 3, 5 mg·kg-1 ,i. p. ) increased the sleep onset to 62. 5%and 87. 5% in subthreshold dosage of sodium pentobar-bital(25 mg·kg-1,i. p. ) treated mice. H057(≥60 mg· kg-1 , i. p. ) could completely induce LORR in mice. The latency of LORR at dose of 60 mg · kg-1 was (24 ± 11) min and the duration of LORR was (96 ± 15 ) min. In vivo mircodialysis revealed that H057 (25 mg·kg-1 , i. p. ) could significantly increase the GABA level by 26% and decrease the 5-HT and NE levels by 50% and 38% in cerebral cortex in mice. Conclusion H057 has potent sedative and hypnotic effects, which may be closely related to the increased content of GABA and the decreased contents of 5-HT and NE in the extracellular fluid in cerebral cortex.

13.
Chinese Medical Journal ; (24): 2583-2587, 2014.
Article in English | WPRIM | ID: wpr-241618

ABSTRACT

<p><b>BACKGROUND</b>Minimal residual disease (MRD)-directedmodified donor lymphocyte infusion (mDLI) is used to treat relapse after hematopoietic stem cell transplantation (HSCT). For patients who experience an unsatisfactory response tomDLI, relapse is usually inevitable. Therefore, we sought to evaluate the efficacy ofinterferon α therapy in these patients.</p><p><b>METHODS</b>Regular MRD monitoring was carried out after the HSCT. The patients who were MRD-positive underwent mDLI. Patients with an unsatisfactory response to mDLI received interferon α therapy (3 million units, twice weekly) with regular monitoring of MRD. To ensure the immunomodulatory effects of interferon α, immunosuppressant treatment would be stopped before interferon α treatment.</p><p><b>RESULTS</b>Five patients with an unsatisfactory response to mDLI treatment received interferon α (3 had t (8;21) chromosomal translocation acute myeloid leukemia, and 2 had common acute leukemia). They had significantly reduced or resolved MRD. Four patients developed chronic graft-versus-host disease. Two of the 5 patients reported transient fevers, and no significant bone marrow suppression was observed. All of them were in continuous complete remission after interferon a treatment. The median survival time was 469 days (range 368-948 days).</p><p><b>CONCLUSIONS</b>In patients with an unsatisfactory response to MRD-directed mDLI, interferon a may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.</p>


Subject(s)
Female , Humans , Male , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Interferon-alpha , Therapeutic Uses , Neoplasm, Residual , Drug Therapy , Therapeutics
14.
Chinese Journal of Internal Medicine ; (12): 647-650, 2009.
Article in Chinese | WPRIM | ID: wpr-393236

ABSTRACT

theengraftment of neutrophil and platelet after HLA-matched sibling allogeneic blood and marrow transplantation.Duration from diagnosis to trarmplantation was another factor influencing engraftment of platelet.

15.
Basic & Clinical Medicine ; (12)2006.
Article in Chinese | WPRIM | ID: wpr-586466

ABSTRACT

Objective To explore the immunologic composition and T cell function of rhG-CSF mobilized peripheral blood grafts(G-PB) and rhG-CSF primed bone marrow grafts(G-BM) after being mixed in different proportions.Methods T cell subgroups,dendritic cells(DC) and its subsets in G-PB and G-BM were analyzed by multicolor flow cytometry.Immunologic composition of G-PB and G-BM after mixture in different proportions were calculated,lymphocyte proliferation ability and quantities of interleukin-4(IL-4),interferon-?(IFN-?) secretion by T cells in mixture grafts were determined using MTT and sandwich ELISA assays.Results After co-incubation of G-PB with G-BM in different proportions,T cell proliferation in mixture grafts was lower than that of NG-BM and G-PB(P

16.
Chinese Journal of Practical Internal Medicine ; (12)2006.
Article in Chinese | WPRIM | ID: wpr-561919

ABSTRACT

Objective To explore the difference of immunological characteristics between recombination human granulocyte colony-stimulating factor(rhG-CSF)mobilized peripheral blood grafts(G-PB)and steady-state bone marrow grafts(SS-BM).Methods From April to October 2003,G-PB and SS-BM of 15 related donors were collected.T cell subgroups,dendritic cells(DC),monocytes and the expression of CD28 costimulatory molecules on T cells were determined by multicolor flow cytometry.The lymphocyte proliferation ability and the quantities of interleukin-4(IL-4)and interferon-?(IFN-?)secreted by T cells were determined using MTT assays and sandwich ELISA.Results The absolute numbers of monocytes,CD3+,CD4+ and CD8+ T cells,and the ratios of CD4/CD8 in G-PB were significantly higher than those in SS-BM,respectively(P0.05).The quantities of IFN-? and IL-4 secreted by T cells per micromilter in G-PB was significantly higher than those in SS-BM(P0.05).The absolute numbers of DC1 and DC2 in G-PB were significantly higher than those in SS-BM(P0.05).Conclusion It is concluded that the difference of immunological characteristics between G-PB and SS-BM may explain the lower incidence of GVHD and lower relapse rate after SS-BM and G-PB transplantation.

17.
Chinese Journal of Practical Internal Medicine ; (12)2001.
Article in Chinese | WPRIM | ID: wpr-563431

ABSTRACT

Objective To investigate the correlation of monocyte counts prior to the collection of recombinant human granulocyte colony-stimulating factor(rhG-CSF)primed bone marrow grafts(G-BM)with the quantities of CD34+ cells in the grafts.Methods From June 2004 to July 2007,fifty-three healthy donors were treated with rhG-CSF[5 ?g/(kg?d)]injected subcutaneously for five consecutive days.Bone marrow grafts and peripheral blood grafts were harvested on the 4th and 5th day,respectively.The quantities of CD34+ cells and blood routine prior to the collection of the G-BM were determined by flow cytometry and blood analyzer XL2100,respectively.Results The monocyte counts in peripheral blood(PB)of the 53 healthy donors were 896?424 per microliter.The counts of CD34+ cells per microliter and quantities of total CD34+ cells in the bone marrow grafts were 84?45 and(8.22?4.84)?107,respectively.Pearson correlation analysis indicated that the counts of monocyte in the PB correlated positively with the counts of CD34+ cells per microliter(r=0.573,P

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